Valvular Heart Disease Has a Diversity Problem

Treatment of valvular heart disease has made phenomenal strides over the past two decades, but these life-changing gains are not trickling down to everybody. A huge part of the problem is the lack of diversity in trials, which hinders the generalizability of blockbuster results to large swaths of the population, say experts.

The Food and Drug Omnibus Reform Act (FDORA) of 2022, which requires the US Food and Drug Administration to provide guidance on increasing diversity in clinical trials, is poised to change this, but many cardiologists argue that more intentional efforts are needed. Enrollment of women and people from racial/ethnic minority groups in trials of heart valves has remained stagnant despite repeated calls for diversity.

Megan Coylewright, MD, editor of the American College of Cardiology's CardioSmart/Patient Voice Program, said this is not a challenge unique to the valvular field, but that it is exceptionally important given the urgency with which valve disease, severe aortic stenosis, for example, must be identified and treated. However, underrepresentation in clinical trials, and the gaps in care that can result from them, is exceptionally important given the urgency with which severe valve disease, such as aortic stenosis, must be identified and treated.

New performance measures dictate that quality aortic valve intervention must occur within 3 months of diagnosis for this population. That’s helpful, Coylewright told TCTMD, “because in that time period of taking care of patients, there can be different opportunities for us to have implicit bias come into our own care, where we may slow down that process.”

With this heightened sense urgency, “I think that when we meet patients of all backgrounds, of all types, we can understand this is a disease condition where we can't let anything get in the way,” she said.

The Heart of the Problem

Wayne Batchelor, MD (Inova Heart and Vascular Institute, Fairfax, VA), agreed that “there’s a time clock here” when it comes to valve disease.

The way he sees it, the diversity problem starts with who gets diagnosed.

“Most studies have shown that if you actually get to a multidisciplinary heart team, you're probably going to get appropriate care and get a TAVR if you have aortic stenosis and you're symptomatic,” Batchelor told TCTMD, adding that it’s a straightforward condition to identify with proper screening. “It's just that we're missing all those upstream patients. Large swaths of patients are just not being diagnosed either. They're not getting echos or they're getting echos and they're not being referred.”

There are inexplicable differences in the rates of TAVR by zip code that seem to imply that there are disparities in care. Sreekanth Vemulapalli

Sreekanth Vemulapalli, MD (Duke University School of Medicine, Durham, NC), said that, in his view, the biggest need right now is to increase the diversity of patients at the beginning of the care pathway. Exactly where in that time line is tough to pinpoint.

“It's clear that when you look, at least in urban areas, by zip codes, there are inexplicable differences in the rates of TAVR by zip code that seem to imply that there are disparities in care,” he commented to TCTMD. “Why is that? Is it a problem of diagnosis? Is it a problem of access to care? Is it a problem of socioeconomic status? . . . There's a lot of work that has to be done to surmount those barriers, and we don't frankly know a lot about whether there's a problem in diagnosis or not. I'd have to guess there is, but we don't have a lot of data to look at it just yet.”

While it’s true that there are issues with who gets diagnosed in the first place, Coylewright said postdiagnosis discrepancies also run rampant.

“We have studies that demonstrate that once patients are hospitalized with atrial fibrillation or with aortic stenosis or with mitral regurgitation and their problem is identified, they're still treated differently,” she said. “They're less likely to get therapies that they need. And when they do get them, they're very delayed.”

Some of this can be attributed to how patients present, especially since women, for example, tend to show up at a later stage of their disease and require more complex care, Coylewright acknowledged. “But even when controlling for those factors, we see disparities in the receipt of transcatheter and surgical therapies,” she said.

Starting With Clinical Trials

Until the patient population of clinical trials more closely matches that of the real world, it seems unlikely that anything will change.

“If we don't have women, minorities, and good representation, then we may be dealing with data that's just biased or not representative, and that's a problem in terms of safety and efficacy determinations,” Batchelor said.

Importantly, he noted, institutions that participate in clinical trials are typically the ones chosen to use new devices commercially—“a major tailwind” that can indirectly amplify disparities further, according to Batchelor. “All those patients at those sites receive that advantage,” he said. “Whether we realize it or not, by having disparities in clinical trial participation in the device world, we're also creating parallel disparities in commercial access.”

If we don't have women, minorities, and good representation, then we may be dealing with data that's just biased or not representative. Wayne Batchelor

Coylewright said that the trust built within communities by conducting clinical trials with more diversity will inevitably improve the care provided after those drugs and devices become commercially available. “The more that we can engage with diverse patients and their communities in all stages of care, the more we have an opportunity to reduce some of those healthcare disparities,” she said.

Admittedly, all the new, exciting technologies that have emerged for valvular heart disease can be a distraction, Coylewright added. “We may do everything within our talents and time and resources to test these devices, but if they're not accessible to people to use to improve quality of life and length of life, then our studies have been for not.”

Fixing clinical trials is a good place to start because it seems “much more doable” than changing the entire healthcare system, Annetine C. Gelijns, PhD (Icahn School of Medicine at Mount Sinai, New York, NY), told TCTMD. It’s still complicated, she admitted, but there is plenty of momentum in the field right now to make positive change.

Addressing the inequities seen in valvular heart disease care, and in medicine more broadly, can seem overwhelming, Coylewright acknowledged. Even so, she encourages her peers to make a dent where they could. “As with any problem we're trying to tackle, if you can get the best minds in the room and you just take it apart one by one, then I think that's how we can make progress,” she added.

Several Solutions

Coylewright, in a recent presentation on trial diversity at the New York Valves meeting, described several barriers that block many patients from participating in clinical research, including restrictive eligibility criteria, lack of access to trial sites, low health literacy, and mistrust. At the Erlanger Health System (Chattanooga, TN), her team has enacted several community-based efforts like group clinics and providing simple trial documents that are easily understandable to patients of different backgrounds. Recruiting a diverse workforce can also help increase patient diversity, she said.

Coylewright also advocated for building relationships with the hospital administrators tasked with encouraging diversity, equity, and inclusion so as to be proactive during ongoing studies.

“It takes more than just goodwill; it really does take resources,” she said. “And if we are going to respond to this FDA request to meet these goals around diversity, we are going to need to ask for resources.”

It won't just be a measure of how many patients you enroll. It will be a measure of which patients you're enrolling. Megan Coylewright

To help rectify the lack of diversity, Batchelor said it’s important to increase the public’s knowledge of clinical trials, a process that may build trust and give people the confidence to participate. “And we have to put extra effort into underserved populations,” he stressed.

Also, Batchelor recommended expanding trials to new locations beyond the usual sites that take part. “One of the reasons we always get the same clinical trial results is we have almost always the same sites participating in research, and they have a natural demographic that comes to them that gets enrolled,” he said.

Once a trial begins, other solutions could include periodic check-ins to ensure a good patient mix as well as surveys of people who declined to participate, which might help trialists gauge the barriers in the way, he suggested.

“We always assume it's because patients don't trust research, but I have a hunch that there are much more practical reasons,” Batchelor said. “It costs time and money to participate in a trial. You almost have to be in an advantaged position for that not to impact you in a meaningful way.”

More data on who gets valvular heart disease and why might also help, said Vemulapalli. The ongoing PREVUE-VALVE and RURAL studies are going be “really important to try to understand if there are diagnostic disparities,” he said. “If we find that there are substantial percentage of minorities with undiagnosed valve disease and they're not getting care, well, now you have the answer to your question about if there's a diagnostic problem in addition to a therapeutic disparity problem that we've already seen in aortic stenosis.”

Gelijns said she would also like to see more studies collect information on social determinants of health. “Often there are variations in outcomes among patients in the trial,” she said. “And by having data on some of the important social determinants of health, we can see to what extent these factors might explain these variations.”

New FDA Guidance

Only last month did the FDA publish its guidance for clinical trials on diversity action plans prompted by FDORA.

“Participants in clinical trials should be representative of the patients who will use the medical products,” said FDA Commissioner Robert M. Califf, MD, in a press release. “The agency’s draft guidance is an important step—and one of many ongoing efforts—to address the participation of underrepresented populations in clinical trials to help improve the data we have about patients who will use the medical products if approved.”

Notably, Coylewright said, the guidance does not indicate that “every site needs to do everything. And in fact, not every trial needs to represent every demographic.” Because of this, industry has been given “a lot of flexibility about how to play a key role in improving representation in clinical trials without feeling like they're asked to do things that they're not able to deliver on,” she explained.

This flexibility is key because “it's very clear that there's not going to be a one-stop solution for enhancing clinical trial diversity,” Batchelor said. “The only way we can have any hope in making a mark is to approach this from all facets from the very beginning of clinical trial question and protocol design to the last patient enrolled.”

One message is clear for clinical trialists aiming to be the best of the best, according to Coylewright, who stressed, “It won't just be a measure of how many patients you enroll. It will be a measure of which patients you're enrolling. And so it behooves you to get together with your research team and your research coordinators to figure out how you're going to improve diversity in your own recruitment.”